This project seeks to understand the structure and function in pathogenesis of infection of several iron-regulated outer membrane proteins of Neisseria gonorrhoea. These proteins are located on the surface of the gonococcus, and may be important to development of a vaccine for the gonococcus which is one of the principal goals of the STD CRC. There are four specific aims. In Aim 1, a molecular mutant of the gonococcal will be created, and this mutant will be used to infect human volunteers in collaboration with investigators in Project 3. This will help to determine, for the first time in any bacterial organism, whether specific ability to utilize human transferrin as a source of iron is required for ability to cause infection. The transferrin-binding proteins are of interest to gonococcal vaccine development and these studies will contribute towards understanding of whether that goal can be achieved. The second specific aim is to understand the regulation and function, as well as vaccine potential, of a major iron-repressed outer membrane protein designated FrpB. Specific Aim 3 seeks to understand the roles in pathogenesis and in iron uptake of several membrane-associated heme-binding proteins. The fourth specific aim seeks to understand the roles in pathogenesis, including attachment and invasion of epithelial cells in vitro of several proteins that are induced by exposure to iron. These studied will enhance our overall understanding of how iron regulates membrane protein composition in the gonococcus and will contribute to understanding of whether iron-regulated proteins might be useful in a gonococcal vaccine.